DRE and PSA are the 2 components necessary for a modern screening program. Transrectal ultrasound (TRUS) has been associated with a high false-positive rate, making it unsuitable as a screening tool, although it is very useful for directing prostatic biopsies.

The indications for screening are controversial. The American Cancer Society recommendations are as follows:
Both prostate specific antigen (PSA) and digital rectal examination (DRE) should be offered annually, beginning at age 50 years, to men who have at least a 10-year life expectancy and to younger men who are at high risk. Information should be provided to patients regarding potential risks and benefits of intervention.

Advocates of screening believe that early detection is crucial in order to find organ-confined disease and, thereby, impact mortality. If patients wait for symptoms or even positive DRE results, less than half have organ-confined disease. Those who do not advocate screening worry that screening will detect some cancers that are not organ confined or that it may find cancers that are not biologically significant. Currently, age-specific PSA cutoffs are used to guide screening. The trend is toward lowering the threshold level to 2.5 ng/dL, but this has not been widely accepted as yet.

Men who choose to undergo screening should begin at age 50 years. Men in high-risk groups, such as those with a strong familial predisposition (2 or more first-degree relatives are affected) and those of African American race, should begin screening at a younger age (40-45 y). These men are less likely to have the latent form of the disease and benefit from treatment. More data on the precise age to start prostate cancer screening are needed for men at high risk.

Recent data from Canadian and Austrian studies suggest that mortality rates are lower as a result of PSA screening. Canadian data have shown that from 1989-1996, the mortality rate was lower in the PSA-screened cohort than the control group. Recent studies from Tyrol, Austria also show a beneficial result for screening in reducing disease-specific mortality. These beneficial effects are likely due to the fact that treatment rather than observation may enhance disease-specific survival. This was recently shown in a 2002 Scandinavian study that reported significantly reduced disease-specific mortality for radical prostatectomy patients when compared with watchful waiting. No difference in overall survival was noted. Currently, US data have shown a decrease in mortality of 1% per year since 1990, which coincides with the advent of PSA screening. Other theories have been proposed to account for the decrease, and these include changing treatment practices and artifacts in mortality rates secondary to the changing incidence.

Abnormal rectal examination findings
Findings from the DRE are crucial. An irregular, firm prostate or nodule is typical, but many cancers are found in prostates that feel normal. Pay careful attention to the prostate consistency, along with the seminal vesicles and adjacent organs, to detect spread of the disease to these structures.

Overdistended bladder due to outlet obstruction

• Neurologic findings secondary to cord compression: Other subtle findings, such as paresthesias or wasting, are uncommon.
• Lower extremity lymphedema
• Supraclavicular adenopathy
• Lower extremity deep venous thrombosis
• Cancer cachexia

Transrectal ultrasound
TRUS is used to examine the prostate for hypoechoic areas, which are commonly associated with cancers but are not specific enough for diagnostic purposes. At least 6 or, more recently, 10 or more systematic biopsy specimens of peripheral and, occasionally, transitional zones are taken under ultrasound guidance. Samples should include most areas of the gland, irrespective of ultrasonographic abnormalities.

Differential diagnosis
Benign prostatic hypertrophy
Calculi
Prostatic cysts
Prostatic tuberculosis
Prostatitis

© Dan Theodorescu
© Tracey L Krupski

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Prostate cancer is the most common noncutaneous cancer among males. Lung cancer and bronchial cancer account for 37% of male cancer deaths, and prostate cancer and colon cancer account for another 10% each. The diagnosis and treatment of prostate cancer continue to evolve. With the development of prostate-specific antigen (PSA) screening, more men are identified earlier as having prostate cancer. While prostate cancer can be a slow-growing cancer, thousands of men die of the disease each year. Education is important to help men understand the risk of progression and the various treatment options. This article provides a current overview of the biology, pathology, diagnostic techniques, natural history, and screening for this disorder.

Incidental findings
In the modern era, most patients present because of abnormalities in a screening PSA level or digital rectal examination (DRE) and not because of symptoms (see Prostate-Specific Antigen). However, prostate cancer can be an incidental pathologic finding when tissue is removed at the time of transurethral resection for obstructive prostatic symptoms.

Elevated PSA level
PSA is a single-chain glycoprotein that has chymotrypsinlike properties. PSA slowly hydrolyzes peptide bonds, thereby liquifying semen. The upper limit of normal for PSA is 4 ng/mL. Some advocate age-related cutoffs, such as 2.5 ng/mL for the fifth decade of life, 3.5 ng/mL for the sixth decade of life, and 4.5 ng/mL for the seventh decade of life. Others advocate race-specific reference ranges. Using recent data from screening studies, some have advocated upper limits of normal of 2.5 ng/mL instead of 4 ng/mL.

Percent of free PSA
A recent development, the measurement of bound and free PSA can help discriminate between patients with mildly elevated PSA levels from cancer and those with benign prostatic hyperplasia. The lower the ratio of free-to-total PSA, the higher the likelihood of cancer. Free PSA is reported as a percent. Using 25% as the cutoff, 95% of cancers can be detected in both African Americans and whites. A cutoff of 22% maximizes cancer detection and minimizes unnecessary biopsies. Generally, these percents are useful in patients who have a PSA level in the range of 4-10 ng/mL.

This information is most useful in men with very large glands or in men who have already had one negative biopsy result. If the man is healthy and has a PSA level of 4-10 ng/mL, many recommend biopsy directly, without the additional free-PSA test, or consider a trial of antibiotic therapy for 4-6 weeks before repeating the PSA test. If antibiotic therapy lowers the PSA to normal levels in a short time, prostate cancer is less likely to have caused the prior elevation, and the PSA test should be repeated in a few months.

Abnormal DRE findings
Various factors are taken into consideration when performing a DRE. A nodule is important, but findings such as asymmetry, difference in texture, and bogginess are important clues to the patient’s condition and should be considered in conjunction with the PSA level. Change in texture over time can offer important clues about the need for intervention. Cysts or stones cannot be accurately differentiated from cancer based on DRE findings alone; therefore, maintain a high index of suspicion if the DRE results are abnormal. In addition, if cancer is detected, the DRE findings form the basis of clinical staging of the primary tumor (ie, T stage in the TNM staging system). In current practice, most patients diagnosed with prostate cancer have normal DRE results but abnormal PSA readings.

Local symptoms
In the pre-PSA era, patients with prostate cancer commonly presented with local symptoms. Urinary retention occurred in 20-25%, back or leg pain occurred in 20-40%, and hematuria occurred in 10-15%. Currently, with PSA screening, patients report urinary frequency (38%), decreased urine stream (23%), urinary urgency (10%), and hematuria (1.4%). However, none of these complaints is unique to prostate cancer and each could arise from a variety of other ailments. Forty-seven percent of patients are asymptomatic.

Metastatic symptoms
Metastatic symptoms include weight loss and loss of appetite; bone pain, with or without pathologic fracture (because prostate cancer, when metastatic, has a strong predilection for bone); and lower extremity pain and edema from nodal metastasis obstructing venous and lymphatic tributaries. Uremic symptoms can occur from ureteral obstruction caused by local prostate growth or retroperitoneal adenopathy secondary to nodal metastasis.

Frequency
With the advent of PSA screening, a greater number of men require education about prostate cancer and how it is diagnosed, staged, and treated in order to select the most appropriate treatment.

According to recent figures from the American Cancer Society, 220,900 new cases were diagnosed in 2003 and 28,900 men will die of prostate cancer . Prostate cancer is rarely diagnosed in men younger than 40 years, and it is uncommon in men younger than 50 years.

Prevalence rates of prostate cancer remain significantly higher in African American men than in white men, while the prevalence in Hispanic men is similar to that of non-Hispanic white men. Hispanic men and African American men present with more advanced disease, most likely related to external (eg, income, education, insurance status) and cultural factors. In addition, African American men generally have higher levels of testosterone, which may contribute to the higher incidence of carcinoma.

Between 1989 and 1992, incidence rates of prostate cancer increased dramatically, probably because of earlier diagnoses in asymptomatic men as a result of the increased use of serum PSA testing. In fact, the incidence of organ-confined disease at diagnosis has increased because both PSA testing and standard DRE are performed. Prostate cancer incidence rates are currently declining, with peak rates in 1992 among white men and in 1993 among African American men.

During 1992-1996, mortality rates for prostate cancer declined significantly, approximately 2.5% per year . Although mortality rates are continuing to decline among white and African American men, mortality rates in African American men remain 2.3 times as high as rates in white men based on 2003 American Cancer Society projections.

Prostate cancer is also found during autopsies performed following other causes of death. The rate of this latent or autopsy cancer is much greater than that of clinical cancer. In fact, it may be as high as 80% by age 80 years.

The prevalence of clinical cancer varies regionally, and these differences may be due to some of the genetic, hormonal, and dietary factors discussed in the next section. High rates are reported in northern Europe and North America, intermediate rates are reported in southern Europe and Central and South America, and low rates are reported in eastern Europe and Asia.

Interestingly, the prevalence of the latent or autopsy form of the disease is similar worldwide. Together with migration studies, this suggests that environmental factors, such as diet, may play a significant promoting role in the development of a clinical cancer from a latent precursor.

© Emedicine.com

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